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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Interferon-alpha receptor-1 (IFNAR1) variants are associated with protection against cerebral malaria in The Gambia
Genes and Immunity, Volume 4, No. 4, Year 2003
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Description
The chromosome 21q22.11 cytokine receptor cluster contains four genes that encode subunits of the receptors for the cytokines interleukin-10 and interferon-alpha, -beta and -gamma that may have a role in malaria pathogenesis. A total of 15 polymorphic markers located within these genes were initially genotyped in 190 controls and 190 severe malaria cases from The Gambia. Two interferon-alpha receptor-1 (IFNAR1) gene SNPs (17470 and L168V) showed evidence for an association with severe malaria phenotypes and were typed in a larger series of samples comprising 538 severe malaria cases, 338 mild malaria cases and 562 controls. Both the 17470-G/G and L168V-G/G genotypes were associated with protection against severe malaria, in general, and cerebral malaria, in particular (P = 0.004 and 0.003, respectively). IFNAR1 diplotypes were then constructed for these two markers using the PHASE software package. The (17470-G L168V-G/17470-G L168V-G) diplotype was found to be associated with a reduced risk of cerebral malaria and the (17470-C L168V-C/17470-G L168V-G) diplotype with an increased risk of cerebral malaria (overall 3 × 2 χ2 = 12.8, d.f. = 2, P = 0.002 and 3 × 2 χ2= 15.2, d.f. = 2, P = 0.0005, respectively). These data suggest a role for the type I interferon pathway in resistance to cerebral malaria. © 2003 Nature Publishing Group All rights reserved.
Authors & Co-Authors
Aucan, Christophe
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Walley, Andrew J.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Hennig, Branwen J.W.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Fitness, Jodene E.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Frodsham, A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Zhang, L.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Kwiatkowski, Dominic P.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Gambia, Banjul
Medical Research Council Laboratories Gambia
Hill, Adrian V. S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Statistics
Citations: 103
Authors: 8
Affiliations: 2
Identifiers
Doi:
10.1038/sj.gene.6363962
ISSN:
14664879
Research Areas
Genetics And Genomics
Infectious Diseases
Study Locations
Gambia